ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.6431A>C (p.Glu2144Ala)

gnomAD frequency: 0.00001  dbSNP: rs754703964
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756890 SCV000884858 uncertain significance not provided 2017-10-20 criteria provided, single submitter clinical testing The p.Glu2144Ala variant (rs754703964) has not been reported in the medical literature or previously identified in our laboratory, but it is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.039% in the Latino population (identified in 13 out of 33,484 chromosomes). The glutamic acid at codon 2144 is moderately conserved considering 12 species (Alamut software v2.10.0), and computational analyses predict that this variant does not affect the structure/function of the USH2A protein (SIFT: tolerated, PolyPhen2: benign, MutationTaster: polymorphism). However, based on the available information, the clinical significance of the p.Glu2144Ala variant cannot be determined with certainty.
Labcorp Genetics (formerly Invitae), Labcorp RCV000756890 SCV001412108 uncertain significance not provided 2022-08-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 2144 of the USH2A protein (p.Glu2144Ala). This variant is present in population databases (rs754703964, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 618477). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV003453541 SCV004181664 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001271996 SCV004181665 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV001271996 SCV001453624 uncertain significance Usher syndrome type 2A 2019-11-11 no assertion criteria provided clinical testing

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